Foretelling Drinking Future From a Buzz

Despite what beer commercials tell you, not everyone responds to alcohol in the same way. For some people, an alcoholic drink is a party-starter, increasing energy and sociability. For others, a drink can be a party-ender, producing feelings of fatigue and sluggishness. In pharmacological terms, alcohol is a mixed stimulant/depressant, able to produce a wide range of behavioral effects. But does an individual’s place on this spectrum of alcohol response predict more than their night on the town? Can it say something about their future potential to binge drink, or abuse alcohol in other ways?

Classically, psychiatrists have linked an individual’s alcohol response to their potential for abuse through one simple word: tolerance. According to the low-level response theory, reduced “intoxicating” effects of alcohol were associated with heavier drinking, as individuals have fewer internal cues warning them to stop. But the experiments that informed the low-level response theory focused on the depressant effects of alcohol, measuring predominantly sedation in test subjects. What about the positive and rewarding effects that inspire some people to drink in the first place?

“What is intoxication? It’s really bi-modal,” said Andrea King, professor of psychiatry and behavioral neuroscience at the Medical Center. “Some people can think intoxication is great – you’re drunk, it’s fun – while others think of it as something bad, that it’s a toxic reaction.”

King studied both of those alcohol responses in a 2002 study, giving heavy and light drinkers a disguised drink in a laboratory and asking the how it made them feel on a variety of measures. The study found that heavy drinkers were indeed more likely to report positive and rewarding effects of alcohol, even when they didn’t know it was alcohol they were drinking. From that small study, King and her team sought to both expand their subject pool and follow participants for years to see how their acute responses in the lab tests might predict their future drinking behavior.

The first data from that epic undertaking – a two-year followup of nearly 200 subjects aged 21 to 35 – was published yesterday in Archives of General Psychiatry. True to King’s hypothesis, an individual’s response to a mystery drink was predictive of how their drinking behavior evolved over the following two years, with both stimulant and sedative effects playing a role. While some subjects who were heavy drinkers at the time of the original experiments curtailed their binge drinking episodes, others demonstrated an “exacerbating” trajectory, binge drinking more frequently – up to half of the days in a month.

The path a subject followed could be foretold by their acute response to alcohol in the lab. Subjects with both higher sensitivity to the rewarding effects of alcohol and lower sensitivity to its depressant effects were found to have the most alcohol problems in the follow-up period. Those subjects drank more and more often, increased the frequency of binge drinking, suffered more alcohol-related consequences, and were more likely to qualify for a diagnosis of an alcohol-use disorder.

“The results change our thinking about how alcohol responses affect the development of an alcohol-use disorder,” King said. “It’s not just overall tolerance, but also sensitivity to alcohol’s euphoric effects that increases risk for excessive drinking.”

This new theory, dubbed a “modified differentiator theory” in King’s paper, could be a game-changer for how substance abuse experts identify people at-risk for alcohol problems. Those who respond very positively to an alcoholic drink might be warned early on that they are at elevated risk for drinking problems.

“If we know more about who’s going to become a problem drinker, we may be able to prevent future escalations and intervene earlier, before development of severe alcoholism,” King said. “The stimulant-type responder could learn that while such a response pattern may not be their fault, it could put them at risk for longer-term problems and consequences.”

One lingering mystery is why the response to alcohol is so different from person to person. Many factors could play a role in increasing alcohol’s rewarding properties or decreasing its negative effects: genetics, prior exposure, or social context. Genetic information collected by King’s team from the study’s heavy and light drinkers may offer some new clues about how a person’s genes can control their alcohol response. But getting at how a person’s early experiences with alcohol might shape how they experience the substance later in life is trickier, thanks to the Illinois Liquor Control Act of 1934.

Because the drinking age is 21 years old, it’s almost impossible to give alcohol to underage subjects in the context of a laboratory study. But it’s common knowledge that binge drinking and other alcohol problems often begin before the legal drinking age, thanks to the temptations of college.

“18 to 20 is the riskiest age range by far and we really need to study this phenomenon in order to prevent it,” King said. “It’s really a challenge…I would like to measure these responses to alcohol in 18-year-olds, because the prevention activities could be very strong at that time.”

Until that kind of study can take place, King’s team continues to collect follow-up information from their subject pool – now 8 years out from their laboratory sessions, and with most now entering their thirties. This unique, ever-growing data set allows the researchers to track the lifetime arc of individual’s drinking behavior, and to trace it back to their unique alcohol response in the original tests.

“We have a rich cohort of drinkers and can look at these things,” King said. “Someone could say that by age 25 if you’re not an alcoholic, maybe you dodged the bullet. But some people develop alcohol dependence beyond those ages, and heavy social drinking behavior is even more prevalent in society than dependence and problematic in its own right. Understanding more about how heavy drinkers’ brains respond differently to alcohol than in low-risk drinkers and how those responses increase future drinking behaviors is crucial.”